HYPOTHALAMO PITUITARY GONADAL AXIS Physiology of the HPG axis - - PowerPoint PPT Presentation

HYPOTHALAMO – PITUITARY – GONADAL AXIS

• Physiology of the HPG axis
• Endogenous opioids and the HPG axis (exercise-

induced menstrual disturbances)

• Effects of the immune system on the HPG axis

(cytokines: interleukins and tumor necrosis factor)

• Hypogonadotrophic hypogonadism :

hyperprolactinemia

HYPOTHALAMUS LHRH : decapeptide

(pattern of administration crucial for pituitary response : pulsatile vs continuous administration)

PITUITARY LH, FSH : glycoproteins composed of 2 chains : α, β α chains are identical β chains are specific for each hormone β chains are biological active

HYPOTHALAMUS LHRH : decapeptide

(pattern of administration crucial for pituitary response : pulsatile vs continuous administration)

PITUITARY LH, FSH : glycoproteins composed of 2 chains : α, β α chains are identical β chains are specific for each hormone β chains are biological active

GONADS

Sex steroids Estrogens Progestins Androgens Gonadal protein hormones inhibins - activins + modulating FSH Follistatins -

ENDOGENOUS OPIOIDS AND MENSTRUAL CYCLE DISTURBANCES

CONCLUSIONS

• Exercise training frequently induces anovulatory

menstrual cycles due to an increase in endogenous

• pioids
• Exercise-induced amenorrhoea increases the risk of

long-term osteoporosis, and may reflect overtraining

• A decrease in percentage body fat inhibits GnRH

through LEPTIN

ENDOGENOUS OPIOIDS DURING PREGNANCY

CYTOKINES : Polypeptides produced by cells from the immune system (macrophages, monocytes, lymphocytes)

interleukins Tumor necrosis factor α Interferon

• Cytokines are not only produced within the immune cells

but also within : – Brain (astrocytes, glial cells, neurones (?) – Hypothalamus – Pituitary gland – Adrenal gland – Gonads – Thyroid gland

PATHOLOGIES OF THE PITUITARY AND HYPOGONADISM

PITUITARY ADENOMAS

• Prolactinomas (PRL)

~ 50 %

• Growth hormone (Acromegaly)

~ 20 %

• ACTH (Cushing)

~ 10 %

• TSH, LH-FSH, Alpha-subunit

rare

• Non functional tumors

~ 15-20 %

PITUITARY ADENOMAS

• Endocrine effects : hyperfunction

hypofunction both combined

• Mass effect : compression of surrounding

structures (neurological, pituitary)

SYMPTOMS OF MASS EFFECTS

• Headache
• Visual field defects : - superior temporal quadranopsia
• bitemporal hemianopsia
• Ophtalmology : lateral extension of adenomas into the

cavernous sinus compromising function of III, IV and VI cranial nerve diplopia

• Rinorrhea
• Pituitary insufficiency

PROLACTINOMA

The most frequent pituitary adenoma : ~ 50 % : microadenoma (<10 mm) : 50 % : macroadenoma (>10 mm) : more frequent

CLINICAL FEATURES IN WOMEN

The classical manifestations of PRL excess :

• amenorrhea and galactorrhea

The gonadal dysfunction can produce any menstrual cycle dysfunction (amenorrhea, oligomenorrhea with anovulation, infertility) Estrogen deficiency may result in

• decreased vaginal lubrification
• decreased libido
• osteopenia

CLINICAL FEATURES IN MEN

Galactorrhea is significantly less frequent than in women Hypogonadism is responsible :

• decreased libido
• impotence
• infertility
• loss of axillary, facial, chest and pubic hair
• slight testicular atrophy
• gynecomasty

DOES HYPERPROLACTINEMIA ALWAYS MEAN THE PRESENCE OF A PROLACTINOMA?

CAUSES OF HYPERPROLACTINAEMIA (I)

• Physiological
• Pharmacological
• Pathological
• Idiopathic
• Other causes

CAUSES OF HYPERPROLACTINAEMIA (II)

Physiological Pregnancy Nursing Nipple stimulation Stress (physical, psychological, hypoglycemia) Exercice Food intake Sleep

CONDITIONS FOR BLOOD SAMPLING IN CASE OF SUSPECTED HYPERPROLACTINAEMIA Blood sampling :

• in a fasting state
• between 8h and 12h
• take 2 - 3 blood samples at 30 min

intervals (stress)

CAUSES OF HYPERPROLACTINAEMIA (III) Pharmacological Numerous drugs stimule PRL Antihypertensive drugs :

• reserpine, a-methyldopa, verapamil

Neuroleptics & antidepressants :

• phenothiazines, butyrophenones, IMAO,

benzamide, imipramine...

CAUSES OF HYPERPROLACTINAEMIA (IV) Pharmacological

Antiemetics : metoclopramide, domperidone Hormones : estrogens (high dosage), TRH Opiates Anti-histaminic : cimetidine Anti-tbc : isoniazide

CAUSES OF HYPERPROLACTINAEMIA (V) Pathological

• Prolactinomas
• Mixed pituitary adenomas : GH + PRL
• Defective hypothalamic dopamine secretion or transport

to the lactotroph :

• Hypothalamic tumors
• Pituitary tumors (pseudoprolactinoma)
• Trauma (stalk section)
• Radiotherapy sequellae

CAUSES OF HYPERPROLACTINAEMIA (VI)

• Stimulation of the lactotroph :
• hypothyroidism (TRH)
• Other causes :
• renal failure
• liver cirrhosis
• diseases of the chest wall
• PCOS
• Macroprolactinaemia (Big - Big PRL)

INVESTIGATIONS OF HYPERPROLACTINAEMIA

When a hyperprolactinaemia is suspected, before further and expensive investigations are proposed, it is necessary to

• Obtain a careful history of drug intake
• Eliminate a primary hypothyroidism
• Control kidney and liver functions
• In women with recent onset of amenorrhea
• r galactorrhea : pregnancy test

DIAGNOSIS OF HYPERPROLACTINAEMIA

Basal PRL levels

• Values >400 ng/ml are virtually diagnostic of prolactinoma
• Values between 100 and 300 ng/ml are usually caused by

a prolactinoma which is radiological evident

• If PRL values < 100 ng/ml : can be difficult !
• There is generally a good correlation between PRL levels

and the size of the adenoma

TRH TEST FOR PRL

• 200 µg TRH i.v.
• Normal response : increase of PRL by > 100 %
• Prolactinoma : no increase, or less than 30 % (macro)

and less than 51 % (micro)

• But does not exclude all forms of functional

hyperprolactinaemia

INVESTIGATIONS OF PROLACTINOMAS

• Basal PRL levels
• TRH stimulation test on PRL (if doubts)
• In case of macroadenoma : test other

anterior pituitary functions

• Imaging
• Visual field